Novel formylpeptide receptor 1/2 agonist limits hypertension-induced cardiovascular damage

Jaideep, Singh, Kristy L, Jackson, Haoyun, Fang, Audrey, Gumanti, Bethany, Claridge, Feng Shii, Tang, Helen, Kiriazis, Ekaterina, Salimova, Alex M, Parker, Cameron, Nowell, Owen L, Woodman, David W, Greening, Rebecca H, Ritchie, Geoffrey A, Head, Cheng Xue, Qin

Cardiovascular Research | 2024

DOI: 10.1093/cvr/cvae103; Cardiovascular Research, 00, 0, 2024-6-16.; Abstract: Aims: Formylpeptide receptors (FPRs) play a critical role in the regulation of inflammation, an important driver of hypertension-induced end-organ damage. We have previously reported that the biased FPR small-molecule agonist, compound17b (Cmpd17b), is cardioprotective against acute, severe inflammatory insults. Here, we reveal the first compelling evidence of the therapeutic potential of this novel FPR agonist against a longer-term, sustained inflammatory insult, i.e. hypertension-induced end-organ damage. The parallels between the murine and human hypertensive proteome were also investigated. Methods and results: The hypertensive response to angiotensin II (Ang II, 0.7 mg/kg/day, s.c.) was attenuated by Cmpd17b (50 mg/kg/day, i.p.). Impairments in cardiac and vascular function assessed via echocardiography were improved by Cmpd17b in hypertensive mice. This functional improvement was accompanied by red